Genome-wide search for genes that modulate inflammatory arthritis caused by Ali18 mutation in mice

Genome-wide search for genes that modulate inflammatory arthritis caused by Ali18 mutation in mice Many of inflammatory diseases, including inflammatory arthritis, are multifactorial bases. The Ali18 semidominant mutation induced by N-ethyl-N-nitrosourea in the C3HeB/FeJ (C3H) genome causes spontaneous inflammation of peripheral limbs and elevated immunoglobulin E (IgE) levels in mice. Although the Ali18 locus was mapped to a single locus on chromosome 4, the arthritic phenotype of Ali18/+ mice was completely suppressed in F1 hybrid genetic backgrounds. To determine the chromosomal locations of the modifier loci affecting the severity of arthritis, an autosomal genome scan of 22 affected Ali18/+ F2 mice was conducted using C57BL/6J as a partner strain. Interestingly, regions on chromosomes 1 and 3 in C3H showed significant genetic interactions. Moreover, 174 N2 (backcross to Ali18/Ali18) and 267 F2 animals were used for measurement of arthritis scores and plasma IgE levels, and also for genotyping with 153 genome-wide single nucleotide polymorphism (SNP) markers. In N2 populations, two significant trait loci for arthritis scores on chromosomes 1 and 15 were detected. Although no significant scores were detected in F2 mice besides chromosome 4, a suggestive score was detected on chromosome 3. In addition, a two-dimensional genome scan using F2 identified five suggestive scores of chromosomal combinations, chromosomes 1 × 10, 2 × 6, 3 × 4, 4 × 9, and 6 × 15. No significant trait loci affecting IgE levels were detected in both N2 and F2 populations. Identification of the Ali18 modifier genes by further detailed analyses such as congenic strains and expression profiling may dissect molecular complexity in inflammatory diseases. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Genome-wide search for genes that modulate inflammatory arthritis caused by Ali18 mutation in mice

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Publisher
Springer-Verlag
Copyright
Copyright © 2009 by Springer Science+Business Media, LLC
Subject
Life Sciences; Zoology ; Anatomy ; Cell Biology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-009-9170-0
Publisher site
See Article on Publisher Site

Abstract

Many of inflammatory diseases, including inflammatory arthritis, are multifactorial bases. The Ali18 semidominant mutation induced by N-ethyl-N-nitrosourea in the C3HeB/FeJ (C3H) genome causes spontaneous inflammation of peripheral limbs and elevated immunoglobulin E (IgE) levels in mice. Although the Ali18 locus was mapped to a single locus on chromosome 4, the arthritic phenotype of Ali18/+ mice was completely suppressed in F1 hybrid genetic backgrounds. To determine the chromosomal locations of the modifier loci affecting the severity of arthritis, an autosomal genome scan of 22 affected Ali18/+ F2 mice was conducted using C57BL/6J as a partner strain. Interestingly, regions on chromosomes 1 and 3 in C3H showed significant genetic interactions. Moreover, 174 N2 (backcross to Ali18/Ali18) and 267 F2 animals were used for measurement of arthritis scores and plasma IgE levels, and also for genotyping with 153 genome-wide single nucleotide polymorphism (SNP) markers. In N2 populations, two significant trait loci for arthritis scores on chromosomes 1 and 15 were detected. Although no significant scores were detected in F2 mice besides chromosome 4, a suggestive score was detected on chromosome 3. In addition, a two-dimensional genome scan using F2 identified five suggestive scores of chromosomal combinations, chromosomes 1 × 10, 2 × 6, 3 × 4, 4 × 9, and 6 × 15. No significant trait loci affecting IgE levels were detected in both N2 and F2 populations. Identification of the Ali18 modifier genes by further detailed analyses such as congenic strains and expression profiling may dissect molecular complexity in inflammatory diseases.

Journal

Mammalian GenomeSpringer Journals

Published: Feb 24, 2009

References

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